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SOX2 and SOX9 are markers of clinically aggressive disease in metastatic high-grade serous carcinoma
- Publication Year :
- 2019
-
Abstract
- Objective The aim of this study was to analyze the expression, biological role and clinical relevance of cancer stem cell markers in high-grade serous carcinoma (HGSC). Methods mRNA expression by qRT-PCR of NANOG, OCT4, SOX2, SOX4, SOX9, LIN28A and LIN28B was analyzed in 134 HGSC specimens (84 effusions, 50 surgical specimens). Nanog, OCT3/4, SOX2 and SOX9 protein expression by immunohistochemistry was analyzed in 52 HGSC effusions. Nanog protein expression in exosomes from 80 HGSC effusions was studied by Western Blotting. OVCAR3 cells underwent CRISPR/Cas9 Nanog knockout (KO), and the effect of Nanog KO on migration, invasion, proliferation and proteolytic activity was analyzed in OVCAR3 and OVCAR8 cells. Results OCT4 mRNA was overexpressed in effusions compared to solid specimens (p = 0.046), whereas SOX9 was overexpressed in the ovarian tumors compared to effusions and solid metastases (p = 0.003). Higher SOX2 and SOX9 expression was associated with primary (intrinsic) chemoresistance (p = 0.009 and p = 0.02, respectively). Higher SOX9 levels were associated with shorter overall survival in univariate (p = 0.04) and multivariate (p = 0.049) analysis. OCT3/4, SOX2 and SOX9 proteins were found in HGSC cells, whereas Nanog was detected only in exosomes. Higher SOX2 protein expression was associated with shorter overall survival in univariate analysis (p = 0.049). OVCAR cells exposed to OVCAR3 NANOG KO exosomes had reduced migration, invasion and MMP9 activity. Conclusions SOX2 and SOX9 mRNA levels in HGSC effusions may be markers of clinically aggressive disease. Nanog is secreted in HGSC exosomes in effusions and modulates tumor-promoting cellular processes in vitro.
- Subjects :
- Adult
0301 basic medicine
Homeobox protein NANOG
Serous carcinoma
Gene Expression
SOX9
Exosomes
Gene Knockout Techniques
03 medical and health sciences
SOX4
0302 clinical medicine
SOX2
stomatognathic system
Cell Movement
Cancer stem cell
Cell Line, Tumor
Biomarkers, Tumor
Humans
Medicine
RNA, Messenger
Neoplasm Metastasis
Aged
Cell Proliferation
Aged, 80 and over
Ovarian Neoplasms
business.industry
SOXB1 Transcription Factors
Obstetrics and Gynecology
SOX9 Transcription Factor
Nanog Homeobox Protein
Middle Aged
medicine.disease
Survival Rate
Blot
030104 developmental biology
Oncology
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Proteolysis
embryonic structures
Cancer research
Immunohistochemistry
Female
Neoplasm Grading
biological phenomena, cell phenomena, and immunity
Neoplasms, Cystic, Mucinous, and Serous
business
Octamer Transcription Factor-3
Subjects
Details
- ISSN :
- 00908258
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....fa3e62ebc67364d8b93f5d5a86a6565f